With the success of receptor-targeted nuclear medicine based agents as well as the influx of new imaging modalities and technologies, there is increasing interest in the development of novel dual-receptor targeted PET agents that have high affinity through multivalency or target two different types of receptors on a single cell. The dual-receptor targeted probes are extremely desirable when both receptors are over-expressed in certain disease but the density of each is relatively low. However, current preparations of such probes require complex organic chemistry, conjugation and radiolabeling strategies, which greatly hinder widespread and routine utilization of promising probes for preclinical and/or clinical studies. Therefore, we are proposing a novel strategy that provides the basis of an efficient, robust and potentially automated platform for the structure optimization and routine production of dual-receptor targeted PET agents for both preclinical and clinical studies. This versatile platform will employ solid-phase synthesis capabilities for preparing PET imaging probes that can target two receptors simultaneously. The solid synthesis platform will significantly facilitate the ease of synthesis by: 1) using a large excess of reactant for fast reactions; 2) increasing the conjugation efficiency via the Staudinger ligation and Cu(I) catalyzed/metal-free click chemistry; 3) radiolabeling and releasing of PET agents from the resins concomitantly; and 4) completely eliminating the need for chromatography purification and significantly increasing specific activity because only radiolabeled agents can be released from the resin and no unlabeled molecule exists in the final PET agent products. By using this platform, dual-receptor targeted PET agents can be obtained in a short time with high specific activity. To validate the synthetic platform, PET agents targeting two low-density receptors that are over-expressed in pancreatic cancer, urokinase plasminogen activator receptor (uPAR) and CXC chemokine receptor 4 (CXCR4), will be prepared and evaluated in cells. In addition, the platform can be easily adapted to prepare multimodal imaging agents for two modalities such as nuclear/optical (or nuclear/magnetic resonance) imaging. If successful, a reliable and robust platform for the rapid preparation of dual-receptor targeted PET agents will be developed. The dual-receptor (uPAR and CXCR4) targeted PET agents will be prepared and evaluated in cells. Combining the advantages offered by dual-receptor targeting strategy and rapid solid-phase platform, the prepared PET agents will provide an excellent opportunity to realize accurate and selective imaging of pancreatic cancer. In a future R01 application, we will develop the automation for scale-up and routine production, perform the structure and reaction conditions optimization, and conduct the comprehensive in vivo evaluation of the dual-receptor targeted PET imaging agents for the early diagnosis of pancreatic cancers.